Clinical and economic outcomes in patients with chronic obstructive pulmonary disease initiating maintenance therapy with tiotropium bromide/olodaterol or fluticasone furoate/umeclidinium/vilanterol

BACKGROUND: Clinical practice guidelines recommend dual long-acting muscarinic antagonists (LAMAs)/long-acting β2agonists (LABAs) as maintenance therapy in patients with chronic obstructive pulmonary disease (COPD) and dyspnea or exercise intolerance. Escalation to triple therapy (TT) (LAMA/LABA/inhaled corticosteroid) is conditionally recommended for patients with continued exacerbations on dual LAMA/LABA therapy. Despite this guidance, TT use is widespread across COPD severities, which could impact clinical and economic outcomes. OBJECTIVE: To compare COPD exacerbations, pneumonia events, and disease-related and all-cause health care resource utilization and costs (in 2020 US dollars) in patients initiating fixed-dose combinations of either LAMA/LABA (tiotropium/olodaterol [TIO + OLO]) or TT (fluticasone furoate/umeclidinium/vilanterol [FF + UMEC + VI]). METHODS: This retrospective observational study of administrative claims included patients with COPD aged 40 years or older initiating TIO + OLO or FF + UMEC + VI from June 2015 to November 2019. TIO + OLO and FF + UMEC + VI cohorts in the overall and maintenance-naive populations were 1:1 propensity score matched on baseline demographics, comorbidities, COPD medications, health care resource utilization, and costs. Multivariable regression compared clinical and economic outcomes up to 12 months in FF + UMEC + VI vs TIO + OLO postmatched cohorts. RESULTS: After matching, there were 5,658 and 3,025 pairs in the overall and maintenance-naive populations, respectively. In the overall population, the risk of any (moderate or severe) exacerbation was 7% lower in FF + UMEC + VI vs TIO + OLO initiators (adjusted hazard ratio [aHR] = 0.93; 95% CI = 0.86-1.0; P = 0.047). There was no difference in the adjusted risk of any exacerbation in the maintenance-naive population (aHR = 0.99; 95% CI = 0.88-1.10). Pneumonia risk was not statistically different between cohorts in the overall (aHR = 1.12; 95% CI = 0.98-1.27) and maintenance-naive (aHR = 1.13; 95% CI = 0.95-1.36) populations. COPD- and/or pneumonia-related adjusted total annualized costs (95% CI) were significantly greater for FF + UMEC + VI vs TIO + OLO in the overall ($17,633 [16,661-18,604] vs $14,558 [13,709-15,407]; P < 0.001; differences [% of relative increase] = $3,075 [21.1%]) and maintenancenaive ($19,032 [17,466-20,598] vs $15,004 [13,786-16,223]; P < 0.001; $4,028 [26.8%]) populations, with significantly higher pharmacy costs with FF + UMEC + VI (overall: $6,567 [6,503-6,632] vs $4,729 [4,676-4,783]; P < 0.001; $1,838 [38.9%]; maintenance-naive: $6,642 [6,560-6,724] vs $4,750 [4,676-4,825]; P < 0.001; $1,892 [39.8%]). CONCLUSIONS: A lower risk of exacerbation was observed with FF + UMEC + VI vs TIO + OLO in the overall population but not among the maintenance-naive population. Patients with COPD initiating TIO + OLO had lower annualized costs than FF + UMEC + VI initiators in the overall and maintenance-naive populations. Thus, in the maintenance-naive population, initiation with dual LAMA/LABA therapy per practice guidelines can improve real-world economic outcomes. Study registration number: ClinicalTrials.gov (identifier: NCT05127304).


Supplementary Table 2. Definitions for censoring of the follow-up period.
The variable period started on the day after the index date, with a minimum of 30-days duration (index date+1 through index date+30) up to a maximum of 12 months duration (index date+1 through index date+365) to assess health-care resource utilization (HCRU), costs, exacerbation, and pneumonia outcomes. Patients were censored at the earliest of the following: discontinuation of the index medication, switch to a non-index regimen, disenrollment from the health plan, 12-months following the index date, or the end of the study period.
• Discontinuation was defined as a gap in therapy of ≥60 days following the runout of days supply (discontinuation date = runout prior to the gap).
Because the discontinuation status of patients whose runout of index medication occurred <60 days before the end of their observation time was unobservable, patients with <60 days of observation time following the runout of their last index prescription claim were flagged as censored, and their observation period ended on the runout date.
• Switch was defined as a pharmacy fill for ≥30 consecutive days of a non-index ICS-, LABA-, or LAMA-containing medication (switch date = first date of the new treatment regimen).
A severe exacerbation was defined as an inpatient admission or an emergency department (ED) visit with a primary COPD diagnosis code or a diagnosis code for acute respiratory failure (ARF) in the primary position plus a COPD diagnosis code in any position, or an inpatient admission or ED visit with a diagnosis code for ARF in the primary position plus an inpatient admission or ED visit with a COPD diagnosis code in any position within ±7 days. A moderate exacerbation involved an ambulatory (office or outpatient) visit with a COPD diagnosis code in any position plus a pharmacy claim for an oral corticosteroid and/or a COPD guideline-recommended antibiotic prescription within ±7 days of the office/outpatient visit.
Exacerbations occurring within 14 days of each other were considered a single exacerbation episode and classified according to the highest severity contributing event.
Abbreviations: COPD, chronic obstructive pulmonary disease. Hypersensitivity pneumonitis due to other organic dusts ICD-10 Dx J679 Hypersensitivity pneumonitis due to unspecified organic dust ICD-10 Dx J680 Bronchitis and pneumonitis due to chemicals, gases, fumes, and vapors ICD-10 Dx J690 Pneumonitis due to inhalation of food and vomit ICD-10 Dx J691 Pneumonitis due to inhalation of oils and essences

ICD version Code Description
ICD-9 Dx 466 Acute bronchitis and bronchiolitis ICD-9 Dx 466.0 Acute bronchitis ICD-9 Dx 466.1 Acute bronchiolitis ICD-9 Dx 466.11 Acute bronchiolitis due to respiratory syncytial virus ICD-9 Dx 466.19 Acute bronchiolitis due to other infectious organisms ICD-10 Dx J20 Acute bronchitis ICD-10 Dx J200 Acute bronchitis due to Mycoplasma pneumoniae ICD-10 Dx J201 Acute bronchitis due to Hemophilus influenzae ICD-10 Dx J202 Acute bronchitis due to streptococcus ICD-10 Dx J203 Acute bronchitis due to coxsackievirus ICD-10 Dx J204 Acute bronchitis due to parainfluenza virus ICD-10 Dx J205 Acute bronchitis due to respiratory syncytial virus ICD-10 Dx J206 Acute bronchitis due to rhinovirus ICD-10 Dx J207 Acute bronchitis due to echovirus ICD-10 Dx J208 Acute bronchitis due to other specified organisms ICD-10 Dx J209 Acute bronchitis, unspecified organism ICD-10 Dx J21 Acute bronchiolitis ICD-10 Dx J210 Acute bronchiolitis due to respiratory syncytial virus ICD-10 Dx J211 Acute bronchiolitis due to human metapneumovirus ICD-10 Dx J218 Acute bronchiolitis due to other specified organisms ICD-10 Dx J219 Acute bronchiolitis, unspecified organism    Adjusted for race/ethnicity, baseline pharmacy claim count, baseline SAMA/SABA pharmacy claim count, and baseline length of COPD-related inpatient stays.
a Defined as utilization with a diagnosis for COPD in any position or a pharmacy claim for a COPD-related treatment, including COPD guideline-recommended antibiotics b Counted as one hospitalization per admission (regardless of length of stay), one visit per day for emergency room visits, and one visit per provider per day for other types of visits c Other medical visits may include services such as independent laboratory, home health, durable medical equipment, etc. Annualized population averages are calculated as the ([sum of all utilization for all individuals during the follow-up period]/[sum of follow-up on-treatment time in years (365 days) for all individuals]). Wald 95% confidence limits for this ratio used the Taylor expansion to estimate the standard error Abbreviations: CI, confidence interval; COPD, chronic obstructive pulmonary disease; FF+UMEC+VI, fluticasone furoate+umeclidinium+vilanterol; HCRU, healthcare resource utilization; TIO+OLO, tiotropium+olodaterol